Genetic diseases that are inherited. Medical genetic examination

Diseases with a hereditary predisposition are diagnosed quite often. Hereditary predisposition to a disease is increased risk its occurrence in a child of a sick mother or father. In other words, if a mother or father suffers from any disease, it can be passed on to their born child, and the development of pathologies that are characterized by a hereditary predisposition occurs when exposed to external factors.

The basis of hereditary predisposition is the genetic uniqueness of the organism, which is manifested in its individual reaction to external factors.

Types of diseases with hereditary predisposition

There is a hereditary predisposition to certain diseases:

1. Monogenic.

Monogenic diseases are based on one mutant gene. Development occurs under the influence of a specific external factor. These include the body’s reaction to medications, dust, food additives, and weather conditions.

2. Polygenic.

Polygenic diseases with a hereditary predisposition have a basis with several genes that are normal rather than altered. Their mutation is observed under the same influence of factors external environment. Almost 90% of all chronic diseases are polygenic diseases non-infectious nature. These include coronary disease, diabetes mellitus, and peptic ulcer disease.

Let's take a closer look at which diseases have a hereditary predisposition.

Cystinuria

Hereditary diseases include cystinuria.

Cystinuria is common congenital anomaly. The cause is a mutation in the Slc3a1 gene. For a child to develop the disease, it is enough to inherit one mutated gene from each parent.

In other words, the disease is caused by the occurrence of stones in the kidney(s). At the same time, a person develops renal colic and more rarely, renal failure. The risk zone for disease of this organ includes children (from 10 years old) and adults up to 30 years old. Symptoms such as abdominal pain, arterial hypertension.

Treatment of such a disease in a child and an adult is primarily aimed at reducing the concentration of cystine so that there is no further education stones in the bladder and kidneys. Yes, recommended drinking plenty of fluids, which will help dissolve cystine.

Cystine dissolves well in an acidic environment. To achieve the required urine pH, special medications are prescribed. But it is worth noting that such drugs increase the risk of such a component in the urine and kidneys as alkali stone.

If conservative treatment is ineffective, resort to surgical intervention. At acute syndrome renal failure Kidney transplantation is recommended.

flat feet

Is flat feet inherited? There is a myth that flat feet is a hereditary disease and if one of the parents had it, then future children will definitely inherit it. This is not true, because only a predisposition to the disease can be transmitted. The development of flat feet can occur under the influence of many factors: wearing the wrong shoes when the foot begins to deform, systematic loads on the feet, etc. But it can also be prevented by following some rules, which we will consider below.

Symptoms of flat feet may include:

• rapid fatigue of the feet;
• swelling that occurs at the end of the day;
• muscle cramps;
• postural deformation;
• quick wearing of shoes on the inside of the foot.

Treatment consists of massage, therapeutic and physical training complex. Orthopedic insoles are useful in this case, the type of which is determined by the doctor, based on the course of the disease and its type.

Plantar (plantar fasciitis)

Such diseases include plantar (plantar) fasciitis. Basically, plantar fasciitis, or, in other words, heel spur, is an acquired disease. But there is also an innate conditioning factor, which is weakness connective tissue, which significantly increases the risk of overloading the foot ligaments.

When the disease occurs, there is a sharp pain in the heel area, which is observed when stepping on the foot. In the first stages of the disease, pain only bothers you in the morning, when a person gets out of bed and takes his first steps. The pain goes away during the day and comes back later prolonged immobility limbs. There may also be a difference in leg length, but it is minor.

An x-ray can reveal a bone growth on the heel, which should be removed as quickly as possible. Treatment primarily involves unloading the feet: eliminating excess weight, flat feet, limitation of physical activity. In this case, insoles are simply irreplaceable and have the same effect.

If severe pain syndrome is observed, painkillers are prescribed. To reduce inflammation, taking non-steroidal drugs is effective. Physiotherapy procedures are also prescribed to help relieve pain and relieve inflammation.

Scoliosis

The disease consists of the formation physiological bending spine in a pathological direction to the side. In this case, rotation of the spinal bodies and progression of the disease with changes in the age and growth of the child are observed.

There are cervical, cervicothoracic, thoracic, thoracolumbar and lumbar scoliosis. The symptoms are as follows: spinal deformity, asymmetrical position of the folds on the buttocks and legs, impaired functioning internal organs, flat feet, difference in limb length (one limb is shorter than the other).

To eliminate such symptoms as different leg lengths, orthopedic insoles and insoles are used. But in any case, different leg lengths are corrected only when the underlying disease, scoliosis, is cured. Thus, to correct different leg lengths and eliminate other symptoms, physiotherapy, massage and exercise therapy are carried out.

Syndactyly

The next type of disease of this kind is syndactyly. The genetically determined disease syndactyly is an abnormal development of the fingers, or rather, their fusion. The cause is a violation of the separation of the fingers during the period embryonic development fetus

A tendency to such deformation of the fetal fingers is observed in those women who have experienced harmful effects, including x-rays, as well as infection of the body during pregnancy.

The symptoms of the disease are clearly expressed: non-separation of the fingers, differences in their length and thickness, which can lead to tightness of the child and depression. Treatment is usually surgical, during which the fused fingers are separated. After the operation, the fingers can exist and function separately from each other.

Ischemia

Coronary heart disease is a disorder of the functioning of the organ, which is a consequence of insufficient oxygen supply to the heart muscle through coronary arteries. A common cause is atherosclerosis of the arteries.

Symptoms of the disease include: arrhythmia, weakness, nausea, shortness of breath, increased sweating, pain syndrome in the heart area with irradiation to nearby areas, human mental disorders (panic, anxiety, melancholy).

Treatment of the disease consists of eliminating the pain syndrome special drugs, taking other medications prescribed by a doctor, and getting proper rest.

There is also a tendency in children to develop a hereditary disease such as diabetes. This disease is endocrine disease, which occurs as a result of the absence or insufficient release of the hormone insulin in the body or its inability to be absorbed by internal organs. Factors that give impetus to the development of the disease are:

• overweight;
• presence of pancreatic pathology;
• disturbed metabolism;
• maintaining a sedentary lifestyle;

• stress;
• alcohol;
• the occurrence of pathologies in the body that reduce immunity;
• the use of drugs that have a diabetogenic effect.
• Symptoms of a disease with a hereditary predisposition are as follows:
• frequent trips to the toilet;
• constant thirst, which leads to dehydration;
• weight loss;
• weakness and fatigue;
• visual system disorder;
• feeling of numbness in the limbs;
• heaviness in the legs;

• dizziness;
• low body temperature;
• the occurrence of cramps in the calf muscles;
• itchy skin syndrome in the perineum;
• heartache.

A common symptom is liver dysfunction, which occurs regardless of the type of disease. This is observed due to an increase in blood glucose levels. At untimely treatment The disease causes the death of liver cells, which are replaced by connective tissue. In this case, liver cirrhosis occurs.

Typically, diabetes is incurable disease, but if you maintain normal blood sugar levels, you can prevent or reduce complications. To do this, a diet is prescribed, which consists of limiting the consumption of sugar-containing foods, as well as foods containing fats and cholesterol. Equally important is maintaining moderate exercise.

The doctor also prescribes glucose-lowering medications, which are taken every day.

Hereditary diseases include stomach ulcers. But this is not always inherited. Thus, only 40% of parents with this disease will have children with ulcers. Factors provoking the disease include:

1. Medicines that a person takes for a long time. These include Aspirin, Diclofenac and other drugs with non-steroidal anti-inflammatory effects. IN old age There is a risk of getting sick when taking such drugs together with coagulants and glucocorticoids.
2. The presence of tuberculosis, syphilis, diabetes mellitus, lung cancer, liver cirrhosis, and pancreatitis in the body increases the risk of ulcers.
3. Injury to the abdominal area (blow, bruise, burn, frostbite).
4. Exposure to the body of the bacterium Helicobacter pylori, which can be infected through a kiss, dirty hands, common utensils, as well as from mother to fetus.

The symptoms of a stomach ulcer are as follows:

1. Abdominal pain syndrome. The pain is usually mild in intensity, but in some cases it can be severe. Increased pain is observed when drinking alcohol, spicy and smoked foods, and during physical activity.
2. The occurrence of heartburn (burning in the epigastric region), which occurs in almost 80% of people suffering from this disease. Heartburn is a process when the acidic contents of the stomach enter the lumen of the esophagus. The occurrence of this symptom is observed 2 hours after eating.
3. Decreased appetite.
4. Nausea occurs. In some cases, nausea and vomiting occur, which is a consequence of impaired gastric motility.
5. Heaviness in the stomach after eating.
6. The appearance of belching.

Treatment of stomach ulcers, first of all, consists of maintaining proper nutrition. Thus, it is unacceptable to consume spicy, hot and rough foods, as well as alcohol.

Treatment with medications consists of taking antibiotics, antacids, gastroprotectors, and reparatives. If the ulcer is multiple or recurrent, or if complications arise, surgery is prescribed. The operation consists of gastric resection and vagotomy - cutting the nerves that stimulate the secretion of acids in the stomach.

In any case, a genetically determined disease can be avoided by following some rules that will help achieve this.

Light-receiving structures of the eye.

The retina of the eye consists of several layers, its thickness is 0.1-0.2 mm.

The outer layer is pigment cells containing fuscin pigment; it absorbs light and prevents its scattering; in strong light, the grains of pigment cells move and shield the rods and cones from the bright light.

Then there is a layer of rods and cones, they are visual receptors - photoreceptors. The photoreceptors of the retina contain light-sensitive substances: rods - rhodopsin, or visual purple (red), cones - iodopsin (violet).

In bright light, the restoration of rhodopsin does not keep pace with its breakdown, and the cones become the light-perceiving receptors. Thus, rods are the apparatus of twilight vision, and cones are the apparatus of daytime vision.

Conductive section of the visual analyzer.

When examining the back wall of the eyeball (i.e., the fundus of the eye) using a specially concave ophthalmoscope mirror, you can see the area from which the blood vessels diverge and the optic nerve emerges. This is the area from which the blood vessels diverge and the optic nerve emerges. This area is called the blind spot because it does not contain rod and cone neuroepithelium. Approximately in the center of the retina is the fovea - this is the place of best vision. It contains only cones.

Area around fossa painted in yellow and is called yellow spot.

The optic nerve fibers arising from the retina intersect on the basal surface of the brain.

Muscular apparatus of the eye.

Is of great importance for normal vision.

The eye is constantly moving as a result of contraction of the muscles of the eyeball.

Eye muscles:

sets the eye for the best vision.

help determine direction

estimate the distance and size of an object

In bright light, the pupil narrows as a result of contraction of the annular muscles, and less light rays enter the retina. In the dark, the pupil dilates due to contraction of the radial muscles. This process is the adaptation of the eye to the strength of light.

Protective apparatus of the eye.

In mammals, the eye is protected by eyelids:

The top reflexively closes

Bottom for irritation

Rudeminated third cornea

Along the edges of the eyelids are glands that secrete ocular lubricant, which, when blinking, spreads over the eyeball and protects it from drying out and prevents tears from rolling down over the edge of the eyelid.

Lacrimal apparatus:

lacrimal glands of the upper and 3rd eyelids

tear ducts

lacrimal sac

tear duct

The glands secrete tears, which moisturize and cleanse the conjunctiva and cornea of ​​the eye. Tears contain lysozyme (a bactericidal substance).

The cornea, lens, and vitreous body do not have blood vessels, so the cells of these tissues receive nutrients from intraocular fluid, filling the anterior and posterior chambers of the eye. The iris and ciliary body have many blood vessels and nutrients from the blood pass into the chambers of the eye. But only those substances that are part of the aqueous humor penetrate through the walls of blood vessels, and its composition differs from the composition of blood.

This property of the walls of the blood vessels of the eye - to let some through and retain others is called hemato-ophthalmic, or eye, barrier.

Topic 18. PHYSIOLOGY OF ADAPTATION

Adaptation is the adaptation of organisms to life through properties that ensure their survival and reproduction in a changing external environment.

According to ecological-geneticclassifications subdivided:

species (inherited) individual (purchased)

Adaptation criteria serve as reactions of the cardiovascular and respiratory systems, blood picture, gastrointestinal functions, state of water metabolism, body temperature.

Adaptation mechanisms.

In the process of adaptation, the animal body reacts as a single whole with the participation of all its organs and systems, with the leading role of the central nervous system. Installed exclusively important in the body's adaptation sympathetic nervous system.

In the development of general adaptation of the body, it is of great importance pituitary-adrenal system. The set of reactions of the body in response to stimulation of this system is called adaptation syndrome, or stress.

WITH stress stage

Alarm reaction Resistance stage Exhaustion stage

The first stage of the “alarm reaction” is characterized by activation of the adrenal glands and the release of catecholamines and glucocorticoids into the blood.

The second stage is the “stage of resistance” - the body’s resistance to a number of extreme irritants increases.

The third stage, the “exhaustion stage,” occurs when stress continues.

Adaptation of animals in industrial complexes.

Crowded housing of animals does not provide the physiologically necessary for them motor activity. Physical inactivity and a high level of irregular feeding create conditions for obesity in cows, which serves as a predisposing factor in the development of ketosis, barrenness and other pathologies, which indicates incomplete physiological adaptation.

Control tests.

Test on topic No. 1 “Blood system”

Write the terms based on the definitions of the corresponding concepts:

The main transport system of the body, consisting of plasma and suspended in it shaped elements.

The liquid part of the blood that remains after the formed elements have been removed from it.

The physiological mechanism that ensures the formation of a blood clot.

Nuclear-free formed elements of blood containing hemoglobin.

Formed elements of blood that have a nucleus and do not contain hemoglobin.

The body's ability to protect itself from foreign bodies and substances.

Blood plasma devoid of fibrinogen.

The phenomenon of absorption and digestion of microbes and other foreign bodies by leukocytes.

A preparation of ready-made antibodies formed in the blood of an animal that was previously specifically infected with this pathogen.

A weakened culture of microbes introduced into the body of animals.

Destruction of red blood cells and release of hemoglobin.

A hereditary disease that is expressed in a tendency to bleed as a result of non-clotting.

Hereditary factor (antigen) found in red blood cells. It was first discovered in macaques.

An animal that receives part of the blood in a transfusion, other tissues or organs in a transplant.

An animal that provides part of its blood for transfusion, other tissues or organs for transplantation into a patient.

A translucent, slightly yellowish alkaline liquid that fills the lymphatic vessels.

The process of formation, development and maturation of blood cells.

0.9% solution Na CL.

Percentage of different types of leukocytes.

Increases during pregnancy with infectious diseases, inflammatory processes.

A parent cell capable of developing into various types of mature cells.

on topic No. 1 “Blood system”

What refers to the internal environment of the body?

A. Intercellular fluid

B. Plasma

B. Serum

2. What refers to the liquid part of blood?

A. Intercellular fluid

B. Plasma

B. Serum

3. What has the ability to attach and release oxygen?

A. Table salt

B. Fibrin

B. Hemoglobin

G. Fibrinogen

D. Antibodies

E. Calcium salts

G. Leukocytes

4. What blood components form the body's immune system?

A. Red blood cells

B. Platelets

V. Fibrin

G. Fibrinogen

D. Leukocytes

E. Hemoglobin

G. Antibodies

5. What is involved in blood clotting?

A. Red blood cells

B. Platelets

V. Fibrin

G. Fibrinogen

D. Leukocytes

E. Hemoglobin

G. Antibodies

6. What structural features are characteristic of leukocytes, and what functions do they perform?

A. There is no core

D. There is a core

D. Flat round shape

E. Transport oxygen

G. Destroy bacteria

7. What structural features are characteristic of erythrocytes and what functions do they perform?

A. There is no core

B. They move amoeboidally, change shape

D. There is a core

D. Flat round shape

E. Transport oxygen

G. Destroy bacteria

8.What cells and substances transport oxygen?

A. Plasma

B. Platelets

B. Leukocytes

G. Fibrin

D. Red blood cells

E. Fibrinogen

J. Hemoglobin

9.What cells are characterized by phagocytosis?

A. Plasma

B. Platelets

B. Leukocytes

G. Fibrin

D. Red blood cells

E. Fibrinogen

J. Hemoglobin

10. How can we explain that it is large? cattle don't have Sap?

A. Natural innate species immunity

B. Natural acquired immunity

B. Artificial immunity

D. There are platelets

D. There are red blood cells

11.Which organs are hematopoietic?

A. Red bone marrow in cancellous bone

B. Yellow bone marrow in the cavities tubular bones

B. Liver

D. Lymphatic glands

D. Heart

E. Stomach

J. Spleen

12. What are the functions internal environment organism?

A. Humoral regulation

B. Motor

B. Nervous regulation

G. Transport

D. Protective

E. Cell nutrition

Scheme on topic No. 2 “Immune system”

Using the reference diagram, characterize the immune system.

AND municipality

Congenital Acquired

(non-specific protective factors) (specific protective factors)

- skin - immune system response

- mucous membranes

- inflammation of lymphocytes

- phagocytosis (neutrophils

monocytes) B cells T cells

cell antibodies

humoral cellular

discovered by Ehrlich

Acquired immunity

Natural Artificial

passive active passive active

(immunity (after illness)

newborn) vaccine

serum colostral (weakened

(ready-made antibodies) (with colostrum from the mother) microbes or their poisons)

Leukocytes

Nonspecific Specific (thymic

Spleen

Lymph nodes

red bone

Phagocytes Lymphocytes

identifiers

(eaters)

T cells B cells

T-helpers (helpers)

Cell T-suppressors (suppress)

Immunity T-killers (killers)

Humoral interferon Plasma cells Memory cells

Immunity

Lysozyme Antibodies

Testing knowledge on topic No. 3 “Blood and lymph circulation system”

What is a cardiac cycle? What phases does it consist of?

Explain the terms “diastole” and “systole”.

Why does blood move in one direction in the heart?

Why is the heart able to work continuously throughout life?

What is cardiac automatism?

How does the strength and frequency of heart contractions change during physical activity?

In what state are the valves of the heart during the contraction of the atria, ventricles, during a pause?

How does the nervous system control the functioning of the heart?

What is the importance of abundant blood supply to the heart muscle?

The walls of the right ventricle are thinner than the left. How can we explain this?

The contraction of which parts of the heart (atria or ventricles) lasts longer? How can you explain their unequal duration of work?

What is the conduction system of the heart, and what is its role in the automaticity of the heart?

Does the same amount of blood pass through the left and right sides of the heart? Why can't this number be different?

The experience of the German physicist Goltz is known when he caused a cardiac arrest with a sharp blow to the belly of a frog. How to explain this fact?

In the proposed list of statements, select the correct ones and write down the numbers under which they are written.

Every cell in the body needs nutrients, oxygen, and water to survive.

In organisms with an open circulatory system the cells are washed directly by the blood.

In organisms with an open circulatory system, blood pressure is usually high and blood flows quickly.

Lymph is a colorless liquid formed from blood plasma by filtering it into the intercellular space and from there into the lymphatic system.

Functions of circulating blood: transport, regulatory, protective.

The heart muscle cannot stimulate the heart to contract.

Cardiac muscle has a structure identical to skeletal muscles.

The thickness of the walls of the atria and ventricles is the same throughout the heart.

The atria are the lower chambers of the heart that receive blood returning from the pulmonary circulation.

The largest blood vessel is the aorta.

Heart contractions are regulated only by impulses originating in the heart itself.

The lymphatic system is a collection of nodes, vessels and lymphoid tissue.

Systolic pressure is the blood pressure at the moment the ventricles relax.

Aneurysm is an expansion of the lumen of the arteries due to protrusion of its wall.

Hypertension is low blood pressure.

The maximum speed of blood movement is created in the aorta and arteries.

The pulse is a rhythmic oscillation of the walls of the veins that arises due to changes in pressure in the vessels in the rhythm of the heart contraction.

Adrenaline is a hormone that dilates blood vessels.

Chemoreceptors are receptors that sense blood pressure in the walls of the aorta and carotid arteries.

The movement of blood in the veins is ensured low pressure, activities skeletal muscles and the presence of pocket-shaped valves.

The arterial pulse of cattle at rest averages 60-80 beats per minute.

Physiological dictation.

Arteries are vessels that carry blood. . .

Veins are the vessels that carry blood. . .

Arrange the blood vessels in order of decreasing blood flow velocity. ..

Arrange the blood vessels in order of decreasing pressure in them. . .

What type of muscle tissue makes up the heart muscle?

Blood pressure at the moment of contraction of the ventricles is called. . .

Blood pressure during ventricular relaxation is called. . .

Blood pressure readings are expressed in two numbers: the smaller one shows ..... pressure, the larger one - . . .

The rhythmic contraction of the arterial walls with each systole of the left ventricle is called. . .

A wave of increased pressure, accompanied by acceleration of blood flow and expansion of arterial walls, is called.....

Main function of heart valves. . .

Determine location:

A) tricuspid valve (….);

B) two-leaf (….);

B) semilunar valves (...).

13. Name the two main vessels that transport blood from the heart (….).

14. Name the arteries that transport blood to the lungs (….).

15. Why does the left ventricle have a thicker muscle wall? (……).

16. Name the types of blood vessels….

17. Name the layers that form the walls of the artery (...)

18. Which layer of the artery walls prevents damage? ...

19. What is the function of the middle layer of artery walls? (…).

20. What type of blood vessels has walls consisting of a single layer of endothelial cells? ...

21. Blood returns to the heart through the veins at low pressure. What feature of the structure of the veins ensures the movement of blood through them? (…).

22. Name the arteries that supply blood to the heart muscle. (….).

23. What chamber of the heart does the aorta depart from? (…..).

24. What is the cardiac cycle? (….).

25. The cardiac cycle consists of:

26. Which part nervous system regulates the duration of the heart? (…).

27. Name the specialized structures of the heart that cause rhythmic contractions and act as conduction systems:

28. Define the pulse.

29. What is the cause of pulse?

On Control questions

studies disciplines"Culturology" directed on formation the following competencies: ... professional spheres. Given educational allowance will allow students understand more deeply theoretical... For example, anatomy, pathology and physiology maybe one...

Today, gynecologists advise all women to plan their pregnancy. After all, in this way many hereditary diseases can be avoided. This is possible with a thorough medical examination of both spouses. There are two points in the question of hereditary diseases. The first is a genetic predisposition to certain diseases, which manifests itself as the child grows up. For example, diabetes mellitus, which one of the parents suffers from, can appear in children in adolescence, and hypertension - after 30 years. The second point is directly genetic diseases with which the child is born. They will be discussed today.

The most common genetic diseases in children: description

The most common hereditary disease in children is Down syndrome. It occurs in 1 case out of 700. The diagnosis of the child is made by a neonatologist while the newborn is in the maternity hospital. In Down syndrome, the child's karyotype contains 47 chromosomes, that is, the extra chromosome is the cause of the disease. You should know that both girls and boys are equally susceptible to this chromosomal pathology. Visually, these are children with a specific facial expression who are lagging behind in mental development.

Girls are more often affected by Shereshevsky-Turner disease. And the symptoms of the disease appear at the age of 10-12: patients are short in stature, the hair on the back of the head is low-set, and at the age of 13-14 they do not experience puberty and no periods. These children show a slight delay mental development. The leading symptom of this hereditary disease in adult woman is infertility. The karyotype for this disease is 45 chromosomes, that is, one chromosome is missing. The prevalence rate of Shereshevsky-Turner disease is 1 case in 3000. And among girls up to 145 centimeters tall, it is 73 cases in 1000.

Only males are affected by Kleinfelter's disease. This diagnosis is established at the age of 16-18 years. Signs of the disease are tall height (190 centimeters or even higher), mild mental retardation, disproportionately long arms. The karyotype in this case is 47 chromosomes. A characteristic symptom for an adult man is infertility. Kleinfelter's disease occurs in 1 in 18,000 cases.

Manifestation is enough known disease- hemophilia - usually observed in boys after one year of life. Mostly representatives of the stronger half of humanity suffer from pathology. Their mothers are only carriers of the mutation. Blood clotting disorder is the main symptom of hemophilia. This often leads to the development of severe joint damage, for example, hemorrhagic arthritis. In hemophilia, any injury that cuts the skin causes bleeding, which can be fatal for a man.

Another hard one hereditary disease- cystic fibrosis. Typically, children under one and a half years of age need to be diagnosed to detect this disease. Its symptoms are chronic inflammation of the lungs with dyspeptic symptoms in the form of diarrhea, followed by constipation and nausea. The frequency of the disease is 1 case per 2500.

Rare hereditary diseases in children

There are also genetic diseases that many of us have never heard of. One of them appears at the age of 5 years and is called Duchenne muscular dystrophy.

The carrier of the mutation is the mother. The main symptom of the disease is the replacement of skeletal striated muscles with connective tissue that is incapable of contraction. In the future, such a child will face complete immobility and death in the second decade of life. Not for today effective therapy Duchenne muscular dystrophy, despite many years of research and the use of genetic engineering.

Another rare genetic disease is osteogenesis imperfecta. This is a genetic pathology of the musculoskeletal system, which is characterized by deformation of the bones. Osteogenesis is characterized by a decrease in bone mass and increased fragility. There is an assumption that the cause of this pathology lies in congenital disorder collagen exchange.

Progeria is a fairly rare genetic defect that results in premature aging body. There are 52 cases of progeria recorded worldwide. Up to six months, children are no different from their peers. Then their skin begins to become wrinkled. The body manifests itself senile symptoms. Children with progeria usually do not live beyond the age of 15. The disease is caused by gene mutations.

Ichthyosis is a hereditary skin disease that occurs as a dermatosis. Ichthyosis is characterized by a violation of keratinization and is manifested by scales on the skin. The cause of ichthyosis is also a gene mutation. The disease occurs in one case in several tens of thousands.

Cystinosis is a disease that can turn a person into stone. The human body accumulates too much cystine (an amino acid). This substance turns into crystals, causing hardening of all body cells. The man gradually turns into a statue. Typically, such patients do not live to see their 16th birthday. The peculiarity of the disease is that the brain remains intact.

Cataplexy is a disease that has strange symptoms. At the slightest stress, nervousness, nervous tension suddenly all the muscles of the body relax - and the person loses consciousness. All his experiences end in fainting.

Another strange and rare disease is extrapyramidal system syndrome. The second name of the disease is the dance of St. Vitus. Her attacks overtake a person suddenly: his limbs and facial muscles twitch. As it develops, extrapyramidal system syndrome causes changes in the psyche and weakens the mind. This disease is incurable.

Acromegaly has another name - gigantism. The disease is characterized by high human stature. And the disease is caused excess production somatotropin growth hormone. The patient always suffers from headaches and drowsiness. Acromegaly today also has no effective treatment.

All these genetic diseases are difficult to treat, and more often they are completely incurable.

How to identify a genetic disease in a child

The level of modern medicine makes it possible to prevent genetic pathologies. To do this, pregnant women are asked to undergo a series of studies to determine heredity and possible risks. In simple words, genetic analyzes are done to identify the propensity of the unborn baby to hereditary diseases. Unfortunately, statistics record an increasing number genetic abnormalities in newborns. And practice shows that most genetic diseases can be avoided by treating them before pregnancy or by terminating a pathological pregnancy.

Doctors emphasize that the ideal option for future parents is to test for genetic diseases at the stage of pregnancy planning.

Thus, the risk of transmitting hereditary disorders to the unborn baby is assessed. To do this, a couple planning a pregnancy is advised to consult a geneticist. Only the DNA of future parents allows us to assess the risks of giving birth to children with genetic diseases. In this way, the overall health of the unborn child is predicted.

The undoubted advantage of genetic analysis is that it can even prevent miscarriage. But, unfortunately, according to statistics, women most often resort to genetic testing after a miscarriage.

What influences the birth of unhealthy children

So, genetic tests allow us to assess the risks of having unhealthy children. That is, a geneticist can state that the risk of having a baby with Down syndrome, for example, is 50 to 50. What factors influence the health of the unborn child? Here they are:

1. Age of parents. With age, genetic cells accumulate more and more “damages”. This means that the older the father and mother, the higher the risk of having a baby with Down syndrome.
2. Close relationship of parents. Both first and second cousins more likely are carriers of the same disease genes.
3. The birth of sick children to parents or direct relatives increases the chances of having another baby with genetic diseases.
4. Chronic diseases of a familial nature. If both father and mother suffer, for example, from multiple sclerosis, then the likelihood of the disease affecting the unborn baby is very high.
5. Parents' belonging to certain ethnic groups. For example, Gaucher's disease, manifested by bone marrow damage and dementia, is more common among Ashkenazi Jews, Wilson's disease - among the peoples of the Mediterranean.
6. Unfavorable external environment. If future parents live near a chemical plant, a nuclear power plant, or a cosmodrome, then polluted water and air contribute to gene mutations in children.
7. Exposure to radiation on one of the parents also increases the risk of gene mutations.

So, today, future parents have every chance and opportunity to avoid the birth of sick children. A responsible attitude towards pregnancy and its planning will allow you to fully experience the joy of motherhood and fatherhood.

Especially for - Diana Rudenko

Along with diseases clearly determined by heredity (genes and chromosomes) or environmental factors (trauma, burns), there is a large and diverse group of diseases, the development of which is determined by the interaction of certain hereditary influences (mutations or combinations of alleles) and the environment. This group of diseases is called diseases with hereditary predisposition.

The causes and features of the development of these diseases are very complex, multi-level, not fully understood and different for each disease. However, it is generally accepted that there are common features in the development of such diseases.

The basis of hereditary predisposition to diseases is a wide genetically balanced polymorphism of human populations with enzymes, structural and transport proteins, as well as antigenic systems. In human populations, at least 25-30% of loci (out of approximately 40,000) are represented by two or more alleles. So, individual combinations of alleles are incredibly diverse. They ensure the genetic uniqueness of each person, expressed not only in abilities and physical differences, but also in the body’s reactions to pathogenic environmental factors. Diseases with a hereditary predisposition occur in individuals with the corresponding genotype (combination of “attractive” alleles) in the event of provoking environmental influences.

Diseases with a hereditary predisposition are conventionally divided into the following main groups: congenital malformations; mental and nervous diseases are common; Midlife illnesses are common.

Most common birth defects development is splitting upper lip and palate, hip dislocation, clubfoot, etc. To mental and nervous diseases with hereditary predisposition include schizophrenia, epilepsy, manic-depressive circular psychoses, multiple sclerosis and others. Among the somatic diseases of middle age, psoriasis, bronchial asthma, stomach and duodenal ulcers often occur, ischemic disease heart, hypertension, diabetes, etc.

In connection with the success of deciphering the human genome, new scientific achievements have expanded the possibilities of genetic analysis of the mechanisms of the occurrence of diseases with a hereditary predisposition, despite their complexity. The pathogenesis of such a disease is a complex, multifaceted and multilevel process, so the significance of hereditary factors cannot be unambiguously determined in all cases. It is often difficult to separate the factors from each other both in terms of intensity and duration of their action. Understanding the causes and course of diseases with a hereditary predisposition is further complicated by the fact that their development is the result of interaction genetic factors(monogenic or polygenic) with environmental factors very specific or less specific. Only the latest achievements in the study of the genome and the compilation of gene maps of human chromosomes make it possible to approach the identification of the effects of the main abnormal gene.

Each disease with a hereditary predisposition is a genetically heterogeneous group with the same clinical end-points. Within each group there are several varieties due to genetic and non-genetic causes. For example, the group of coronary heart diseases can be divided into several monogenic forms of hypercholesterolemia (high blood cholesterol).

The reasons for the development of diseases with a hereditary predisposition are schematically shown in Fig. 5.19. their quantitative combinations in the development of diseases may be different in different people.

For diseases with a hereditary predisposition to manifest, a specific combination of hereditary and external factors is necessary. The more pronounced the hereditary predisposition and the greater the influence of the environment, the higher the individual’s likelihood of getting sick (at an earlier age and in a more severe form).

Rice. 5.19.

The comparative importance of external and hereditary factors in the development of diseases is shown schematically in Fig. 5.20.

Rice. 5.20.

Three levels of hereditary predisposition and three degrees of environmental influence are conventionally defined: weak, moderate and strong. With a weak hereditary predisposition and minor environmental influences, the body maintains homeostasis and the disease does not develop. However, if the effect is enhanced harmful factors it will appear in a certain part of people. With a significant hereditary predisposition to pathology, the same environmental factors cause illness in a larger number of people.

Diseases with a hereditary predisposition differ from other forms hereditary pathology(genetic and chromosomal) clinical picture. Unlike genetic ones, in which all members of the proband’s family can be divided into sick and healthy, the clinical picture of a disease with a hereditary predisposition has continuous transitions within the same form of pathology.

Diseases with a hereditary predisposition are characterized by differences in their manifestation and severity depending on gender and age. The mechanisms of spread of such diseases over time are quite complex, since in populations both genetic characteristics of susceptibility and environmental factors can change in different directions.

A feature of diseases with a hereditary predisposition is an increased frequency (accumulation) in certain families, due to their genetic constitution. Figure 5.21 shows examples of pedigrees burdened with hypertension (a) and allergic diseases (b). Genealogical analysis of such pedigrees makes it possible to accurately determine the prognosis of the course of pathology in the family, as well as therapeutic and preventive measures against it.

Rice. 5.21.

Hereditary predisposition to the disease may have a monogenic or polygenic basis.

CHAPTER IX. Hereditary human diseases

9.1 Concept, classification and features of hereditary pathology

Pathology is any deviation from the normal course of biological processes - metabolism, growth, development, reproduction.

Hereditary pathology is a deviation from the norm with an established fact of inheritance, that is, transmission from generation to generation. It is necessary to distinguish between congenital pathology - present from the birth of the individual - and hereditary pathology. Congenital pathology can be caused by the action of environmental factors - lack of nutrients and oxygen during intrauterine development, birth injuries, infections, and so on. Establishing, in accordance with the requirements of genetic analysis (Chapter II), the fact of inheritance of an abnormal trait is the only basis for recognizing the hereditary nature of the pathology.

There are two types of classification of hereditary pathology. The first (accepted mainly in domestic literature) – clinical type. According to this type of classification, there are four groups of diseases:

Group I is actually hereditary diseases - chromosomal and gene diseases (Edwards and Patau syndromes, phenylketonuria, cystic fibrosis);

Group II – diseases with a pronounced hereditary predisposition, in the pathogenesis of which the manifestation of hereditary factors is determined by the action of specific external circumstances (arterial hypertension, diabetes mellitus, gout);

Group III– diseases that are determined primarily by environmental factors, but in the pathogenesis of which hereditary factors play some role (glaucoma, atherosclerosis, breast cancer);

Group IV - diseases to which heredity at first glance has no relation ( food poisoning, fractures, burns).

It should be noted that the frequently used concepts of “familial” and “sporadic” diseases are not directly related to heredity. Familial diseases are observed in relatives, but can also be caused by the action of the same external reasons, for example, the nature of nutrition. Sporadic cases occur in individual individuals, but may also be due to a rare combination of alleles or a de novo mutation.

The second classification system - genetic - is generally accepted in foreign literature and has recently been increasingly found frequent use and in literature in Russian. According to this system, five groups are distinguished:

Group I – gene diseases determined by mutations in certain genes. These are predominantly monogenic traits with autosomal dominant, autosomal recessive, sex-linked dominant, sex-linked recessive, holandric and mitochondrial modes of inheritance (Chapter II);

Group II – chromosomal diseases, that is, genomic and chromosomal mutations (Chapter V);

Group III – diseases with a hereditary predisposition, in the pathogenesis of which environmental and hereditary factors that have a monogenic or polygenic type of inheritance (myopia, morbid obesity, gastric ulcer) play a role.

Group IV – genetic diseases of somatic cells, often associated with malignant neoplasms(retinoblastoma, Wilms tumor, some forms of leukemia);

Group V – diseases of genetic incompatibility between mother and fetus, which develop as a result of the mother’s immune reaction to fetal antigens (incompatibility for the Rh factor and some other erythrocyte antigen-antibody systems).

Hereditary diseases can begin to manifest themselves in at different ages. The nature of the manifestation (the time of manifestation of the first symptoms of the disease) is specific for different forms hereditary pathology. As a rule, hereditary diseases are characterized by a chronic (long-term) progressive (with an increase in the severity of symptoms) course.

9.2 Chromosomal diseases

This group includes diseases caused by abnormalities in the number or structure of chromosomes. About 1% of newborns have an abnormal karyotype, and among stillborns, the incidence of aberrations in the number or structure of chromosomes is 20%. General characteristic features chromosomal diseases are: low weight at birth, developmental delay, short stature, microcephaly, micrognathia, osteogenesis disorders, abnormal eye position. More detailed description chromosomal diseases are given in sections 5.8 and 5.9.

9.3 Gene diseases

Genetic diseases are pathological conditions caused by gene mutations. Most often, this concept is applied to monogenic diseases.

This group is characterized by heterogeneity - the same diseases can be caused by mutations in different genes. General principles for the development of pathology at the gene level can be:

Production of an abnormal protein product;

Lack of normal protein;

An insufficient amount normal protein;

Excess of normal protein product.

According to the nature of violations of homeostasis (the constancy of the internal environment of the body), the following groups of gene diseases are distinguished:

1. Diseases of amino acid metabolism.

The largest group of hereditary metabolic diseases. Almost all of them are inherited in an autosomal recessive manner. The cause of diseases is the insufficiency of one or another enzyme responsible for the synthesis of amino acids.

Phenylketonuria- impaired conversion of phenylalanine to tyrosine due to a sharp decrease in the activity of phenylalanine hydroxylase - an autosomal recessive disease. It appears at the age of 2-4 months, the first symptoms are lethargy, cramps, eczema, “mouse” smell (smell of ketones). Severe brain damage gradually develops, leading to a sharp decrease in intelligence up to idiocy. If from the first days of life you completely exclude (or significantly limit the amount) phenylalanine from the diet of a sick child before puberty, symptoms do not develop. The disease is caused by mutations in the gene PAH, which encodes phenylalanine 4-hydroxylase. Gene PAH localized to HSA12q24.1. Several dozen mutations of this gene have been described in different populations. There are PCR-based diagnostic systems that can detect heterozygous carriage. Recently, new approaches to the treatment of phenyketonuria have been developed - replacement therapy with phenylalanine lyase, a plant enzyme that catalyzes the breakdown of phenylalanine into harmless metabolites, and gene therapy by inserting the normal phenylalanine hydroxylase gene into the genome.

Alkaptonuria– an autosomal recessive disorder of tyrosine metabolism and accumulation in body tissues ( articular cartilage, tendons) homogentisic acid. Manifestation occurs in childhood. The first symptom is darkening of the urine. Often develops urolithiasis disease and pyelonephritis. The accumulation of homogentisic acid breakdown products leads to joint damage (primarily the knee and hip). There is darkening and increased fragility of the connective tissue. Darkening of the sclera and ears is characteristic. Mutations in the gene HGD Homogentisic acid oxidases are the cause of this disease. This gene contains 14 exons and is localized in HSA3q21-23. About 100 different missense, frameshift and splice site mutations have been described and are associated with this disease .

Oculocutaneous albinism 1– absence or significant deficiency of pigment in the skin, hair, iris and pigment membranes of the eye (Figure IX, 1).

Figure IX, 1. A representative of the Negroid race is an albino. Based on materials from the site http://upload.wikimedia.org/wikipediacommons/99a/Albinisitic_man_portrait

A disease with an autosomal recessive type of inheritance. Manifests in varying degrees depigmentation of skin, hair, iris and pigment membranes of the eye, decreased visual acuity, photophobia, nystagmus, frequent sunburn. Various missense, frameshift and nonsense mutations in the tyrosinase gene ( TYR, HSA11q24) are responsible for this disease.

2. Disorders of carbohydrate metabolism

Galactosemia– absence or significant decrease in the activity of the enzyme galactose-1-phosphate-uridyltransferase and accumulation in the blood of galactose and its derivatives, which have a toxic effect on the central nervous system, liver and lens of the eye. In the first days and weeks of life, jaundice, liver enlargement, nystagmus, muscle hypotonia, and vomiting are observed. Over time, cataracts and retardation in physical and mental development develop. Characterized by milk intolerance.

The disease has an autosomal recessive mode of inheritance. Several forms of this disease are caused by different mutant alleles of the gene GALT(galactose-1-phosphate uridyltransferase), localized in the region of HSA9p13. Missense mutations reduce enzyme activity to varying degrees, which determines varying degrees of severity of disease symptoms. For example, Durthe's galactosemia is almost asymptomatic, only a tendency to liver disorders is noted.

Gierke's disease (glycogenosis type I, glycogen disease type I)– inability to convert glucose-6-phosphate into glucose, which leads to disruption of the synthesis and decomposition of glycogen. Glycogen deposition occurs, the reverse process does not. Hypoglycemia develops. The accumulation of excess glycogen in the liver and kidneys leads to liver and kidney failure. The type of inheritance is autosomal recessive. The cause of the disease is a mutation in the gene G6PC, which codes for the enzyme glucose-6-phosphatase. 14 mutant alleles of this gene have been described and are associated with Gierke's disease. There are molecular genetic tests to identify heterozygous carriage and prenatal diagnosis of this disease.

3. Lipid metabolism disorders

Niemann-Pick disease types A and B- decreased activity of the enzyme lysosomal acid sphingomyelinase, which is encoded by the gene SMPD1(HSA11p15.4-p15.1). The type of inheritance is autosomal recessive. Violation of lipid metabolism leads to the accumulation of lipids in the liver, lungs, spleen, and nerve tissues. Characterized by degeneration of nerve cells, disruption of the nervous system, elevated level cholesterol and lipids in the blood. Type A is lethal in early childhood. Type B is more mild; patients usually survive to adulthood. Different types are caused by different mutations in the gene SMPD1.

Gaucher disease (glycosylceramide lipidosis)- accumulation of glucocerebrosides in the cells of the nervous and reticuloendothelial system, caused by deficiency of the enzyme glucocerebrosidase, which is encoded by the gene GBA(HSA1q21). It belongs to the group of lysosomal storage diseases. Some forms of the disease manifest themselves in severe damage to the liver, spleen, nervous and bone tissue.

4. Hereditary diseases of purine and pyrimidine metabolism

Lesch-Nychen syndrome – a sex-linked recessive disease in which the content of uric acid in all body fluids. The consequence of this is developmental delay, mild mental retardation, seizures aggressive behavior with self-harm. Insufficiency of enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase due to mutations in the gene HPRT1(HSAXq26-q27.2) underlies this disease. Several mutations in the same gene have been described, resulting in gout(impaired purine metabolism and deposition of uric acid compounds in tissues).

5. Connective tissue metabolic disorders

Marfan syndrome (spider fingers, arachnodactyly)- connective tissue damage due to a mutation in the gene FBN1(HSA15q21.1), responsible for fibrillin synthesis. Inherited in an autosomal dominant manner. The clinical polymorphism of the disease is explained a large number mutant alleles, each of which can appear in a heterozygous state. Patients are characterized by tall stature, asthenic physique (disproportionately long limbs), arachnodactyly (long thin fingers), weakness ligamentous apparatus, retinal detachment, lens subluxation, prolapse mitral valve(Figure IX, 2).

Figure IX, 2. Marfan syndrome. Based on materials from the site http://www.spineinfo.ru/infosources/case/cases_14.html.

Mucopolysaccharidoses- a group of connective tissue diseases associated with impaired metabolism of acid glycosaminoglycans (mucopolysaccharides) caused by a deficiency of certain lysosomal enzymes. These diseases are classified as lysosomal storage diseases. They manifest themselves in various defects of bone and connective tissue. Mucopolysazaridosis type I (Hurler syndrome) is an autosomal recessive disease resulting from deficiency of the enzyme alpha-L-iduronidase due to mutations in the IDUA gene (HSA4q16.3). This leads to the accumulation of protein-carbohydrate complexes and fats in the cells of the body. As a result, patients experience short stature, significant mental retardation, enlarged liver and spleen, heart defects, cloudy corneas, bone deformities, and coarsening facial features (Figure IX, 3).

Figure IX, 3. Hurler syndrome. Based on materials from the site http://medgen.genetics.utah.edu/photographs/pages/hurler_syndrome.htm.

Mucopolysaccharidosis type II(Hunter syndrome) is a sex-linked recessive disease that is caused by a defect in the enzyme iduronate sulfotase due to a mutation in the IDS gene (HSAXq28). The accumulation substances are dermatan and heparan sulfates. Characterized by rough facial features, scaphocephaly, noisy breathing, low rough voice, frequent acute respiratory viral infections (Figure IX, 4 ) . At the age of 3-4 years, disturbances in coordination of movements appear - the gait becomes clumsy, children often fall when walking. Patients are characterized by emotional lability and aggressiveness. Progressive hearing loss, nodular skin lesions of the back, osteoarthritis, and corneal lesions are also observed.

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Figure IX, 4. Hunter syndrome. Based on materials from the site http://1nsk.ru/news/russia/23335.html.

Mucopolysaccharidosis type III (Sanfilippo syndrome, Sanfilippo disease) - a disease caused by the accumulation of heparan sulfate. It is characterized by genetic heterogeneity - there are 4 types of this disease, caused by mutations in 4 different genes encoding enzymes involved in the metabolism of accumulated substances. The first symptoms of the disease in the form of sleep disturbances appear in children over 3 years of age. Apathy gradually develops, there is a delay in psychomotor development, speech impairment, and facial features become coarse. Over time, children stop recognizing others. Patients are characterized by growth retardation, joint contractures, hypertrichosis, and moderate hepatosplenomegaly. In contrast to Hurler and Hunter syndromes, mental retardation predominates in Sanfilippo disease, and lesions of the cornea and of cardio-vascular system are missing.

Figure IX, 5. Sanfilippo syndrome. Adapted from http://runkle-science.wikispaces.com/Sanfilippo-syndrome.

Fibrodysplasia (myositis ossificans, paraosseous heterotopic ossification, Munheimer's disease)- a connective tissue disease associated with its progressive ossification as a result of a mutation in the gene ACVR1(HSA2q23-q24), which encodes the activin A receptor. The type of inheritance is autosomal dominant. The disease manifests itself birth defects development - primarily with crooked big toes and disorders in cervical spine spine at the level of vertebrae c2 - c7. The disease is progressive in nature and leads to significant impairment functional state musculoskeletal system, profound disability of patients and death, mainly in childhood and young age (Figure IX, 6). The disease is also called “disease of the second skeleton”, since where normal anti-inflammatory processes should occur in the body, bone growth begins.

Figure IX, 6. Fibrodysplasia. Based on materials from the site http://donbass.ua/news/health/2010/02/15.

6. Disorders of circulating proteins

Hemoglobinopathies- hereditary disorders of hemoglobin synthesis. There are two groups of hemoglobinopathies. The first is characterized by a change in the primary structure of the globin protein, which may be accompanied by disturbances in its stability and function (for example, sickle cell anemia). In hemoglobinopathies of the second group, the structure of hemoglobin remains normal, only the rate of synthesis of globin chains is reduced (for example, β -thalassemia).

7. Metabolic disorders in erythrocytes

hereditary spherocytosis- congenital deficiency of erythrocyte envelope lipids. The disease is characterized by an autosomal dominant or autosomal recessive type of inheritance, depending on the gene mutation SPTA1(HSA1q21), which encodes erythrocyte α-1 spectrin. An anomaly of this protein leads to an increase in the concentration of sodium ions inside the erythrocyte, and the penetration of excess water into it due to an increase in osmotic pressure. As a result, spherical red blood cells are formed - spherocytes, which, unlike biconcave normal red blood cells, do not have the ability to change shape in narrow areas of the blood flow, for example, when passing into the sinuses of the spleen. This leads to a slowdown in the movement of erythrocytes in the sinuses of the spleen and the detachment of part of the erythrocyte membrane with the formation of microspherocytes. Destroyed red blood cells are absorbed by macrophages of the spleen. Hemolysis of red blood cells leads to hyperplasia of pulp cells and enlargement of the spleen. One of the main clinical symptoms is jaundice. The main symptoms of hereditary spherocytosis are an enlarged spleen (usually protruding from under the hypochondrium by 2 - 3 cm) and jaundice. Sometimes there are signs of delayed development, disturbances facial skeleton, tower skull, saddle nose, high palate, abnormal alignment of teeth, narrow eye sockets.

8. Hereditary diseases of metal metabolism

Konovalov-Wilson disease (hepatocerebral dystrophy)– an autosomal recessive disorder of copper metabolism, leading to severe damage to the central nervous system and internal organs. The disease is caused by low or abnormal synthesis of ceruloplasmin (a copper transport protein) due to insufficient enzymatic activity of the copper-transporting ATPase. Mutations (about 200 of them have been described) in the gene ATP7B(HSA13q14-q21) lead to changes in the β-polypeptide of this enzyme, which is the genetic basis of this pathology. The main role in the pathogenesis is played by a violation of copper metabolism, its accumulation in the nervous, renal, liver tissues and cornea, resulting in toxic damage copper of these organs. Large-nodular or mixed cirrhosis forms in the liver. In the kidneys, the proximal tubules are primarily affected. In the brain, the basal ganglia, dentate nucleus of the cerebellum and substantia nigra are most affected.

9. Malabsorption in the digestive tract

Cystic fibrosis (cystic fibrosis) - an autosomal recessive disease characterized by damage to the exocrine glands, severe violations respiratory functions and gastrointestinal tract. The cause is gene mutations CFTR(HSA7q31.2), which encodes a transmembrane regulator of cystic fibrosis. The disease is characterized by damage to the exocrine glands, severe dysfunction of the respiratory system and gastrointestinal tract.

Lactose intolerance (hypolactasia) - autosomal recessive pathological condition of poor digestion of lactose ( milk sugar), the genetic basis of which is mutations in the regulatory and coding regions of the gene LCT(HSA2q21), which codes for lactase. This enzyme is expressed predominantly in the ciliated cells of the intestine and is responsible for the breakdown of lactose into galactose and glucose. The main symptoms of lactase deficiency are flatulence, abdominal pain, diarrhea, and vomiting. In children, lactase deficiency may manifest chronic constipation, restlessness and crying after eating. In different human populations, the frequencies of mutant alleles vary from 1 to 100%.

10. Hormonal disorders

Testicular feminization (Morris syndrome) - a sex-linked recessive disease when a male karyotype (46, XY) manifests a female phenotype. expressiveness varies. With incomplete feminization, the gonads develop according to the male type, but some sexual characteristics correspond to the female sex with varying degrees of severity - hypertrophied clitoris, incomplete closure of the scrotal suture, scrotal labia majora, shortened vagina (Figure IX, 7). With complete feminization, the main symptom is the absence of menstruation and sexual hair growth with well-developed mammary glands and a female phenotype. The disease is caused by various mutations in the gene AR(HSAXq11-q12), which codes for the androgen receptor.

Figure IX, 7. View of the external genitalia with incomplete testicular feminization. Based on materials from the site http://www.health-ua.org/img/woman/tabl/8_17.jpg.

Androgenital syndrome (female pseudohermaphroditism) - an endocrine disorder with an autosomal recessive type of inheritance, in which the patient has male external genitalia and a female hormonal structure. Patients have an enlarged clitoris, which becomes similar to a male penis with one urogenital opening, there is no external entrance to the vagina, the labia minora are absent, and the labia majora look like a “cut” scrotum. In this case, the internal genital organs may have a normal appearance. The genetic basis of the disease are gene mutations CYP21(HSA6q21.3), which encodes the enzyme 21-hydroxylase of the cytochrome P450 group, involved in the synthesis of the hormones aldosterone and cortisol.

9.4 Molecular markers in the study of hereditary pathology

A significant part of hereditary diseases and diseases with a hereditary predisposition are not monogenic in nature. They can be classified as quantitative traits, that is, those that have a continuous range of variability and can be measured - for example, height, weight, limb length. Alleles a large number genes contribute to the manifestation of such traits, which is why they are called polygenic. It is possible to trace their inheritance and identify genes whose alleles are involved in pathological processes using genetic markers. Identification of linked inheritance (association) phenotypic traits With genetic markers allows you to find regions of chromosomes that have decisive influence on the processes being studied (positional cloning), and obtain reliable systems for molecular diagnostics (molecular labeling). Currently, the most common markers in human genetics are microsatellite loci (Figure IX, 8; Section 8.1) and mononucleotide polymorphic sites - SNP (Figure IX, 9), the main features of which are shown in Table IX, 1.

Analysis of gene expression (all or a group) on biochips in tissues related to a specific hereditary disease, under normal and pathological conditions, often makes it possible to identify candidate genes for the disease being studied. The chromosomal localization of DNA sequences affecting a quantitative trait (QTL) can be determined based on co-inheritance with several closely spaced markers. If it is possible to find markers that limit the QTL on both sides, then based on the genomic sequence data (Sections 7.7 and 8.4), a list of genes that are positional candidates for the QTL of the disease being studied can be compiled. By combining expression analysis and disease association studies with molecular markers, the most likely candidate genes can be identified—those that will appear on both lists.

The degree of susceptibility to certain drugs and the effectiveness of their use varies widely. For the same disease, the drug suitable for a particular individual is often selected by trial and error. In addition to wasting time, this approach sometimes causes irreparable harm to health. Currently for a large number medicines SNP-based marker systems have been developed that allow a priori (before experience) to predict the response of an individual organism to a particular chemical substance. Associations of individual allelic variants of DNA markers with the characteristics of biochemical reactions are the basis of individual therapy (Figure IX, 10).

Figure IX, 8. In microsatellite loci, the unit of variation is a group of nucleotides.

Figure IX, 9. At mononucleotide polymorphic sites (SNPs), the unit of variation is a single nucleotide.

Table IX, 1. Comparison of the main characteristics of SNPs and microsatellites.

Figure IX, 10. The principle of selecting individual therapy based on polymorphism of mononucleotide repeats - SNP.

Control questions and tasks for chapter IX

1. Which group of hereditary diseases can be attributed to cystic fibrosis?

2. Can a heterozygote for a gene mutation SPTA1 be hereditary spherocytosis?

3. What hereditary disease is caused by the accumulation of heparan sulfate?

4. Why is there four possible SNP alleles?

Additional Reading for Chapter IX

N.P. Bochkov. Clinical genetics // M.: Geotar-Med. 2002. – 457 S.